The Na,K-ATPase is an important membrane-associated enzyme responsible for maintaining the high internal potassium concentration and low internal sodium concentration characteristic of most animal cells. The ion gradients created by the Na,K-ATPase are fundamental to such diverse cellular functions as the regulation of cell volume and pH, the uptake of nutrients and membrane excitability. Because of its pivotal role in ion and water homeostasis, alterations in Na,K-ATPase activity are associated with several cardiovascular, renal and neurological disorders. The present studies will use the techniques of molecular physiology to study the structure, function and regulation of the Na,K-ATPase. This will involve: 1) Identification of the specific amino acids within the alpha subunit that are required for oligomerization; 2) Indentification of the region of the Na,K-ATPase beta subunit that influences cation affinity; 3) Indentification of the amino acids of the gamma subunit that are required for subunit interactions; and finally, 4) Further characterization of cardiac function and cardiac excitability in transgenic mice expressing the Na,K-ATPase gamma subunit. The proposed studies will contribute to a better understanding of this important transport protein.